Development of a hepatic differentiation method in 2D culture from primary human hepatocyte-derived organoids for pharmaceutical research.

ABSTRACT: Human liver organoids derived from primary human hepatocytes (PHHs) are expected to be a hepatocyte source for preclinical in vitro studies of drug metabolism and disposition. Because hepatic functions of these organoids remain low, it is necessary to enhance the hepatic functions. Here, we develop a novel method for two dimensional (2D)-cultured hepatic differentiation from PHH-derived organoids by screening several compounds, cytokines, and growth factors. Hepatic gene expressions in the hepatocyte-like cells differentiated from PHH-derived organoids (Org-HEPs) were greatly increased, compared to those in PHH-derived organoids. The metabolic activities of cytochrome P450 (CYP) 1A2, CYP2C8, CYP2C19, CYP2E1, and CYP3A4 were at levels comparable to those in PHHs. The cell viability o

SUBMITTER: Ueyama-Toba Y 

PROVIDER: S-EPMC11401167 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature